The HIV envelope

Description

Entry of HIV-1 into target cells requires the sequential interaction of the viral envelope glycoprotein gp120 with the CD4 receptor and either CCR5 or CXCR4 acting as co-receptors. The viral envelope is under strong evolutionary pressure along HIV-1 infection due to both innate and adaptive immune responses: chemokines binding HIV-1 co-receptors, neutralizing antibodies and probably class I Interferon, are mechanisms driving important changes in the structure of the HIV-1 envelope in a particular HIV-1 infected patient. In support of this hypothesis it is well known that viral strains binding CCR5 (R5-tropic) and with a resistance to Interferon are preferentially transmitted, and R5-tropic viruses predominate in the early phases of infection. In contrast, those strains that use CXCR4 for entry emerge after years of infection, and this emergence correlates with a poor clinical outcome and development of AIDS. However, up to 50% of the infected individuals progress to AIDS in the presence of only R5 viruses and the mechanisms driving this selection are not fully understood so far.

In the lab we have addressed the study of the HIV-1 envelope from different perspectives and we consider the viral envelope as both a major determinant of HIV pathogenesis and a mirror of the innate and adaptive immune response elicited against HIV.

Different projects and approaches to get a better insight on the characteristics of the HIV-1 envelope are developed by Mayte Pérez-Olmeda (Senior researcher), Javier García-Pérez (Tenure Post-doc) and Nuria González (Tenure Post-doc) with the support of the technicians Almudena Cascajero, Amparo Álvarez and Laura Jiménez.

Development of a vaccine against HIV: Isolation and characterisation of new broad neutralizing antibodies. Design of immunogens able to generate these antibodies (FIS PS09/01459). Principal investigators: P Alcamí and E Yuste (Hospital Clínic, Barcelona). 2010-2012.

Scientific collaborations

Thanks to the development of a new recombinant virus system carrying specific genetic sequences from patients, we had the opportunity of participating in the NEUTNET and EUROPRISE Networks supported by the European Commission. In this initiative we validated our model with gold standards in the field and collaborated closely with Gabriella Scarlatti from Università Vita-Salute San Raffaele, Milan, and Leo Heyndrick from the Instituut voor Tropische Geneeskunde, Antwerp (Fenyö EM, et al. PLoS One. 2009;4(2):e4505. and Heyndrickx L, et al. PLoS One. 2012;7(5):e36438.).

We collaborate with Bernard Lagane and Fernando Arenzana-Seisdedos from Unité de Patologie Virale Molléculaire at Pasteur Institute in the study of the mechanisms driving HIV-1 evolution in vivo, and in particular, the role of chemokines in this process. These projects are funded by the French Agency on AIDS Research, ANRS, (Colin P, et al. Proc Natl Acad Sci U S A. 2013 Jun 4;110(23):9475-80.).

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